NDLI: Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors

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Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors

Content Provider	Scilit
Author	Celver, Jeremy Sharma, Meenakshi Thanawala, Vaidehi Octeau, J. Christopher Kovoor, Abraham
Copyright Year	2013
Description	Journal: Journal of Neurochemistry We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-K(ir)3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825321/pdf
Ending Page	65
Page Count	9
Starting Page	57
e-ISSN	14714159
DOI	10.1111/jnc.12359
Journal	Journal of Neurochemistry
Issue Number	1
Volume Number	127
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2013-07-30
Access Restriction	Open
Subject Keyword	Journal: Journal of Neurochemistry D2 Dopamine Receptor G-protein Coupled Receptor Kinase
Content Type	Text
Resource Type	Article

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